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presenilin

Function: - PS1 & PS2 are involved in the Notch signalling pathway - PS1 contains aspartyl protease activity of APP gamma secretase [3]; PS2 may have a similar role - proteins that interact with presenilins include: a) nicastrin b) catenins (alpha?, beta & gamma) c) cadherins d) calsenilin e) PARL, DOCK3, KCNIP4 - putative substrates* for aspartyl protease activity include: a) amyloid precursor protein (APP) {gamma-secretase} b) amyloid precursor-like proteins (APLP1 & APLP2) c) notch-homolog protein d) Ire-1 protein * specifity may be broad, including many single transmembrane proteins that undergo cytoplasmic domain release from membrane Structure: - PS1 & PS2 contain 7-9 transmembrane domains, most likely 8 - presenilins are similar to C elegans sel-12 gene (suppressor &/or enhancer of lin-12) [2] Compartment: - PS1 & PS2 are associated with membranes of the secretory pathway & appear to be involved in protein trafficking, but may also be associated with the plasma membrane. Pathology: - presenilins PS-1 &/or PS-2 are found as components of neurofibrillary tangles [1], but not neuropil threads or dystrophic neurites (as determined by immunohistochemical staining with antibodies raised to sequences shared by PS-1 & PS-2)

Related

APP gamma-secretase presenilin-like protein

Specific

presenilin-1; PS-1; EC=3.4.23.-; protein S182; contains: presenilin-1 NTF subunit; contains: presenilin-1 CTF subunit; contains: presenilin-1 CTF12; PS1-CTF12 (PSEN1, AD3, PS1, PSNL1) presenilin-2; PS-2; STM-2; E5-1; AD3LP; AD5; contains: presenilin-2 NTF subunit; contains: presenilin-2 CTF subunit (PSEN2, AD4, PS2, PSNL2, STM2)

General

enzyme catalytic subunit glycoprotein membrane protein

Properties

COMPARTMENT: endoplasmic reticulum golgi plasma membrane MOTIF: membrane region

References

  1. Murphy GM Jr, Forno LS, Ellis WG, Nochlin D, Levy-Lahad E, Poorkaj P, Bird TD, Jiang Z, Cordell B. Antibodies to presenilin proteins detect neurofibrillary tangles in Alzheimer's disease. Am J Pathol. 1996 Dec;149(6):1839-46. PMID: 8952521
  2. Levitan D, Greenwald I. Facilitation of lin-12-mediated signalling by sel-12, a Caenorhabditis elegans S182 Alzheimer's disease gene. Nature. 1995 Sep 28;377(6547):351-4. PMID: 7566091
  3. Li YM, Xu M, Lai MT, Huang Q, Castro JL, DiMuzio-Mower J, Harrison T, Lellis C, Nadin A, Neduvelil JG, Register RB, Sardana MK, Shearman MS, Smith AL, Shi XP, Yin KC, Shafer JA, Gardell SJ. Photoactivated gamma-secretase inhibitors directed to the active site covalently label presenilin 1. Nature. 2000 Jun 8;405(6787):689-94. PMID: 10864326
  4. Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev. 2001 Apr;81(2):741-66. Review. PMID: 11274343